The proposed study is based on our accomplishments of the past year. Following three doses of morphine (10, 30, and 50 mg/kg i.p.) treatment, the sensory input was studied extensively in freely behaving rats in four structures (caudate nucleus, substantia nigra, ventromedial hypothalamus and pineal body). Each structure of the four responded differently. Dose related effects were observed in all four structures, while time effects, i.e., change in responsiveness and direction of response (by increase or decrease) with time, were observed only in caudate nucleus. Naloxone (l mg/kg i.p.) reversed the effects of morphine. It is the objective of this project to examine further the effects of morphine with relation to neurotransmitter agents within the central nervous system. This will be accomplished through studying the comparative aspects of structure - function relations during actions of three families of drugs, i.e., depletion, blocking and mimicking of specific neurotransmitters followed by morphine treatment. The first goal is to study the interaction of morphine with 5-HT. The comparative effects of morphine alone, of blocking, mimicking, or depletion of 5-HT only, and the interaction of morphine with the blocking, depletion or mimicking of 5-HT will be examined. The proposed investigation is unique, in that it focuses on elementary processes underlying the organization of the complex neuronal activities, of which the sensory motor and somatosensory subcortical regulatory mechanisms are comprised. The comparative effects of narcotic drugs on neuronal events at various sites of transmission will be determined. This new approach to the study of central narcotic action will provide several kinds of cogent information, specifically where and how acute effects of morphine and related narcotic drugs exert their function on the central nervous system. BIBLIOGRAPHIC REFERENCES: McClung, R.E., Dafny, N., and Burks, T.F. Effects of morphine and naloxone on CNS field potentials in unanesthetized rats. Fed. Proc. 1975, 59: 786. Dafny, N., and Burks, T.F. Morphine modification of evoked potentials in extrapyramidal system. Proc. Soc. Neuroscience, 1975, 5: 285.